Tablets account for approximately 70 percent of all dosage forms sold in the United States, according to Business Communications Co. Inc. Traditionally, tablets have been manufactured by wet granulation followed by drying, sizing, blending/ lubrication and compression of the final granulation. Today, approximately 50 percent of tablets made in the U.S. nutraceutical and pharmaceutical industry are made by direct compression.
Direct compression requires only blending and compression. Reducing the number of unit operations requires less time and energy consumption, and allows for cost advantages both from an operational and capital investment point of view. However, the inherent compactibility of raw materials becomes more important in direct compression. In this regard, direct compression presents a challenge for many poorly compressible nutraceutical actives. The challenge of achieving desirable tablet mechanical properties, such as tablet strength and friability from a poorly compressible high-dose active, can be overcome by selection of an appropriate tablet binder.
An ideal binder should have good binding properties, as determined by compressibility under pressure, high plasticity, low elasticity and small particle size. Small particle size facilitates even distribution of the binder through the inter-particulate void spaces in a tablet. Uniform binder distribution in the tablet results in decreased pore structure and subsequent enhancement in tablet crushing strength. To reduce friability, a binder with highly plastic properties (high deformability) is essential. A further requirement for a good binder is low hygroscopicity. Excessive uptake of moisture (greater than 5 percent) or high moisture content can lead to instability and sticking during production.
There are many excipients used as binders in the direct compression; these include hydroxypropylcellulose (HPC), methylcellulose (MC), povidone (PVP), hydroxypropylmethylcellulose (HPMC), and starches and their derivatives, such as pregelatinized and granulated starches. These polymers differ in their physico-chemical, mechanical and morphological characteristics. For direct compression, studies suggest highly compactable, plastic, fine particle size binders facilitate compression of drugs at relatively low filler-to-drug ratios, therefore representing ideal properties for tablet binders (Drug Dev Ind Pharm. 1999;25:1129-35) (Drug Dev Ind Pharm. 2001;27:181-924).
Formulators should take time to compare different excipients and binders during product development to ensure maximum production value and bioavailability of actives. Comparative testing can reveal significant differences among similar binders in a product matrix. In-house testing by Aqualon compared performance of various binders—including MC, HPMC, PVP, MCC and the company’s Klucel Nutra® D modified cellulose—for a very high-dose Echinacea purpurea raw powder tablet. Tablets were prepared by direct compression and evaluated for hardness, friability and disintegration time. Use of a more efficacious binder allows companies to keep high-dose tablets smaller, eliminating volumes often occupied by low performing or less preferable diluents and fillers.
The choice of a suitable binder for a nutraceutical tablet formulation requires knowledge of the relative importance of binder properties for enhancing the strength of the tablet. Addition of efficient tablet binders offers a single-binder system that provides tablet toughness and low friability at low-use levels, thus minimizing tablet volume of high-active content nutraceuticals.
Murali Divi, Ph.D., is a senior staff scientist and Thomas Durig is the global R&D manager for pharmaceutical excipients and film coatings, both with Aqualon, a business unit of Hercules Inc. Aqualon (Aqualon.com) is a global supplier offering a range of higher performance excipients.